The first stages in the large scale purification of the GTP-regulatory protein involved in activation of adenylate cyclase have been carried out. A simple system using S 49 lymphoma cells lacking this protein has been developed which allows rapid assays of N on a microscale either with neutral detergent extracts of membranes containing N units or even with intact membranes. Turkey erythrocyte membranes proved to have a sufficiently high concentration of N units for purification studies. Modest purification has been achieved on a GTP-sepharose affinity column.